Editing Cell growth (section)

== Mechanisms of cell growth control ==

[[Cell biology|Cells]] can grow by increasing the overall rate of cellular [[biosynthesis]] such that production of [[biomolecules]] exceeds the overall rate of cellular degradation of [[biomolecules]] via the [[proteasome]], [[lysosome]] or [[autophagy]].

[[Biosynthesis]] of [[biomolecules]] is initiated by expression of [[genes]] which encode [[RNA]]s and/or [[proteins]], including [[enzymes]] that catalyse synthesis of [[lipids]] and [[carbohydrates]].

Individual [[genes]] are generally [[regulation of gene expression|expressed]] via [[transcription (biology)|transcription]] into [[messenger RNA]] (mRNA) and [[translation (biology)|translation]] into [[protein]]s, and the expression of each gene occurs to various different levels in a cell-type specific fashion (in response to [[gene regulatory networks]]).

To drive cell growth, the global rate of gene expression can be increased by enhancing the overall rate of [[transcription (biology)|transcription]] by [[RNA polymerase II]] (for active genes) or the overall rate of [[messenger RNA|mRNA]] [[translation (biology)|translation]] into [[protein]] by increasing the abundance of [[ribosome]]s and [[tRNA]], whose [[ribosome biogenesis|biogenesis]] depends on [[RNA polymerase I]] and [[RNA polymerase III]]. The [[Myc]] [[transcription factor]] is an example of a regulatory protein that can induce the overall activity of [[RNA polymerase I]], [[RNA polymerase II]] and [[RNA polymerase III]] to drive global [[transcription (biology)|transcription]] and [[translation (biology)|translation]] and thereby cell growth.

In addition, the activity of individual [[ribosome]]s can be increased to boost the global efficiency of [[messenger RNA|mRNA]] [[translation (biology)|translation]] via regulation of translation initiation factors, including the 'translational elongation initiation factor 4E' ([[eIF4E]]) complex, which binds to and caps the 5' end of [[messenger RNA|mRNA]]s. The protein [[mTOR|TOR]], part of the [[mTORC1|TORC1]] complex, is an important upstream regulator of [[translation (biology)|translation]] initiation as well as [[ribosome biogenesis]].<ref name="Hafen2004">{{cite book|last1=Hafen|first1=E.|title=TOR|chapter=Interplay Between Growth Factor and Nutrient Signaling: Lessons from Drosophila TOR|series=Current Topics in Microbiology and Immunology|volume=279|year=2004|pages=153–167|issn=0070-217X|doi=10.1007/978-3-642-18930-2_10|pmid=14560957|isbn=978-3-642-62360-8}}</ref> [[mTOR|TOR]] is a serine/threonine [[kinase]] that can directly phosphorylate and inactivate a general inhibitor of [[eIF4E]], named [[EIF4EBP1|4E-binding protein (4E-BP)]], to promote translation efficiency. [[mTOR|TOR]] also directly phosphorylates and activates the ribosomal protein S6-kinase ([[S6K]]), which promotes [[ribosome biogenesis]].

To inhibit cell growth, the global rate of gene expression can be decreased or the global rate of [[biomolecular]] degradation can be increased by increasing the rate of [[autophagy]]. [[mTOR|TOR]] normally directly inhibits the function of the [[autophagy]] inducing kinase [[ULK1|Atg1/ULK1]]. Thus, reducing [[mTOR|TOR]] activity both reduces the global rate of [[translation (biology)|translation]] and increases the extent of [[autophagy]] to reduce cell growth.